The major goals of this project are to characterize the host's immune response to helminth infections and to relate these findings to the pathogenesis of clinical disease. Studies of human filariasis (bancrofti) and schistosomiasis (mansoni) suggest that the initial vigorous cellular immune responses to parasite antigens which characterize recently infected individuals are progressively modulated to an essentially unresponsive state during chronic infection. This 'defect' in responsiveness during chronic infection is antigen specific and primarily limited to cellular immunity. Factors responsible for inhibiting this cellular reactivity can be detected both in serum and in mononuclear cell populations. The importance of humoral immunity, especially that associated with IgE antibodies in these helminth infections has been demonstrated both in its relation to the various clinical syndromes of filariasis in man (including tropical eosinophilia) and in its association with protective immunity in rats with brugian filariasis. Subpopulations of eosnophils have been defined by the presence or absence of IgG and complement receptors, and the importance of these receptor-bearing cell populations in specific interactions between eosinophils and parasites (microfilriae and schistosomules) has been demonstrated.